Alternative titles; symbols
HGNC Approved Gene Symbol: DCD
Cytogenetic location: 12q13.2 Genomic coordinates (GRCh38) : 12:54,644,589-54,648,365 (from NCBI)
Todorov et al. (1996) isolated a circulatory catabolic factor that was responsible for the cachexia accompanying murine adenocarcinoma MAC16 by using an antibody cloned from splenocytes of mice transplanted with the MAC16 tumor. The factor was found to be a proteoglycan of relative molecular mass 24 kD, which produced cachexia in vivo by inducing metabolism of skeletal muscle. The 24-kD material was also present in the urine of cachectic patients, as detected on immunoblots with the antibody against the mouse proteoglycan. Todorov et al. (1996) detected immunoreactivity in urine of patients with various types of cancer, particularly pancreatic cancer, but did not find any in the urine of patients with cachexia due to other causes or in the urine of cancer patients without cachexia. The 24-kD proteoglycan was distinguished from the cytokines, not only in structure, but also by its ability to accelerate breakdown of skeletal muscle in vitro and in vivo and to produce weight loss in vivo by a process not involving anorexia.
By screening subtracted primary melanoma and benign melanocytic nevus tissue cDNA libraries with cDNA arrays, Schittek et al. (2001) identified a cDNA encoding dermcidin, or DCD. The 110-amino acid DCD protein contained a sequence resembling the cachectic-associated protein described by Todorov et al. (1996) and a survival-promoting peptide, Y-P30, described by Cunningham et al. (1998). Dot blot analysis showed no detectable expression of DCD. RT-PCR analysis detected DCD expression in skin, melanocytic nevus, and cutaneous melanoma tissue, but not in any other organ systems tested. In situ hybridization and immunodetection analyses demonstrated expression of DCD in the Golgi complex of dark mucous cells of secretory coils in dermal eccrine sweat glands, suggesting that DCD is a secreted protein. High performance liquid chromatography, mass spectrometry, and microsequence analysis of sweat showed a processed 47-amino acid DCD peptide with a calculated mass of 4.7 kD, compared with the expected 9.3 kD of full-length DCD without the signal peptide.
Schittek et al. (2001) found that a synthetic DCD-derived peptide, DCD-1L, composed of 48 C-terminal amino acids of DCD had dose- and time-dependent bactericidal and fungicidal activities in neutral or acidic (sweat-like) buffers. The fungicidal activity occurred at a higher but still physiologic concentration of DCD-1L compared with the bactericidal activity. These results suggested that DCD has a role in innate immune responses in skin.
Using serial analysis of gene expression (SAGE), Porter et al. (2003) identified a SAGE tag that was present only in invasive breast carcinomas and their lymph node metastases. The transcript corresponding to this SAGE tag, DCD, encodes a secreted protein normally expressed only in the pons of the brain and sweat glands. Further studies demonstrated that DCD was overexpressed in approximately 10% of invasive breast carcinomas; in some cases its overexpression was coupled with a copy number gain at its locus (12q13.1), and its expression was associated with advanced clinical stage and poor prognosis. Expression of DCD in breast cancer cells promoted cell growth and survival and reduced serum dependency. Putative high- and low-affinity receptors for DCD were present on the cell surface of breast carcinomas and neurons of the brain. Based on these data, Porter et al. (2003) hypothesized that DCD may play a role in tumorigenesis by means of enhancing cell growth and survival in a subset of breast carcinomas.
Atopic dermatitis (ATOD; see 603165) patients are prone to recurrent bacterial and viral infections and tend to have pronounced skin colonization with Staphylococcus aureus. Rieg et al. (2005) collected exercise-induced sweat from the foreheads of ATOD patients and controls who had not recently washed or been medicated and found that the levels of DCD or DCD-derived peptides, such as DCD1 and DCD1L, were significantly reduced in ATOD patients. Furthermore, DCD levels were even lower in ATOD patients with a history of infectious complications compared with ATOD patients without previous infectious complications. Sweating in healthy subjects led to a 46% reduction of viable skin surface bacteria, whereas sweating in ATOD patients led to only a 3% reduction. Rieg et al. (2005) concluded that decreased expression of DCD and DCD-derived peptides in ATOD patients correlates with clinical infectious complications that may contribute to the propensity of ATOD skin to have recurrent bacterial and viral infections.
Schittek et al. (2001) determined that the DCD gene contains 5 exons and is expressed as a single transcript.
By radiation hybrid analysis, Schittek et al. (2001) mapped the DCD gene to chromosome 12q13. By FISH, Porter et al. (2003) mapped the DCD gene to chromosome 12q13.1.
Cunningham, T. J., Hodge, L., Speicher, D., Reim, D., Tyler-Polsz, C., Levitt, P., Eagleson, K., Kennedy, S., Wang, Y. Identification of a survival-promoting peptide in medium conditioned by oxidatively stressed cell lines of nervous system origin. J. Neurosci. 18: 7047-7060, 1998. [PubMed: 9736629] [Full Text: https://doi.org/10.1523/JNEUROSCI.18-18-07047.1998]
Porter, D., Weremowicz, S., Chin, K., Seth, P., Keshaviah, A., Lahti-Domenici, J., Bae, Y. K., Monitto, C. L., Merlos-Suarez, A., Chan, J., Hulette, C. M., Richardson, A., Morton, C. C., Marks, J., Duyao, M., Hruban, R., Gabrielson, E., Gelman, R., Polyak, K. A neural survival factor is a candidate oncogene in breast cancer. Proc. Nat. Acad. Sci. 100: 10931-10936, 2003. [PubMed: 12953101] [Full Text: https://doi.org/10.1073/pnas.1932980100]
Rieg, S., Steffen, H., Seeber, S., Humeny, A., Kalbacher, H., Dietz, K., Garbe, C., Schittek, B. Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo. J. Immun. 174: 8003-8010, 2005. [PubMed: 15944307] [Full Text: https://doi.org/10.4049/jimmunol.174.12.8003]
Schittek, B., Hipfel, R., Sauer, B., Bauer, J., Kalbacher, H., Stevanovic, S., Schirle, M., Schroeder, K., Blin, N., Meier, F., Rassner, G., Garbe, C. Dermcidin: a novel human antibiotic peptide secreted by sweat glands. Nature Immun. 2: 1133-1137, 2001. [PubMed: 11694882] [Full Text: https://doi.org/10.1038/ni732]
Todorov, P., Cariuk, P., McDevitt, T., Coles, B., Fearon, K., Tisdale, M. Characterization of a cancer cachectic factor. Nature 379: 739-742, 1996. [PubMed: 8602222] [Full Text: https://doi.org/10.1038/379739a0]